This research project seeks understanding of the two components of the factor VIII complex, antihemophilic factor (VIII:C) and the von Willebrand factor (factor VIII-related protein, VIIIR), and the nature of their interaction. Methods will be developed for the immunologic detection of these two proteins in agarose gel systems so that it will be possible to determine their size and charge properties, as well as those of their fragments and the analogous proteins found in CRM-positive hemophilia A and von Willebrand's disease. VII:C will be purified from plasma, its biochemical properties will be determined, and the effect of thrombin on its structure and function will be examined. The interaction of VIII:C with VIIIR will be studied to determine the binding constant, stoichiometry, and effects of pH and ionic strength on association and dissociation. Immunoradiometric assays for the two components of the factor VIII complex will be used to carry out prenatal diagnosis of hemophilia and thereby provide more satisfactory genetic counseling.